Dibromo-maleimide PEG (DBM) consists of a maleimide with a bromine attached to each of the alkene carbons and PEG moiety.
Unlike typical maleimides, DBM allows for two points of attachment since each bromine can be substituted with a thiol to form two thioether bonds. This mild and selective reaction allows for the use of sensitive biomolecular reagents and its high efficiency avoids using excess amounts of expensive biologics.
DBM is used for site-selective conjugation in a controlled manner. The approach uses the interchain disulfide bonds, a native feature to all antibody sub-classes. The two bromo- are excellent leaving groups when react with nucleophilic thiol groups, such as the two cysteines, resulting from the reduction of the disulfide bridge. This insertion of a 2-carbon bridge into a disulfide bond keeps the structural feature intact and maintains the activity of the protein of interest.
The dibromo-mal PEG thio reaction is fast, efficient, high yielding, site specific, and generates stable products that retain their full biological activity. Therefore, represent an ideal approach for homogeneous conjugation products. For instance, doxorubicin was successfully conjugated with trastuzumab using dibromo-maleimide linker. Under optimized controlled sequential methods, DAR 1, 2,3 and 4 can be achieved. The production of homogenous, stable ADCs can be achieved in high yields.
*https://pubs.rsc.org/en/content/articlehtml/2014/ob/c4ob01550a
*https://www.future-science.com/doi/10.4155/tde.15.52
